Two observations, recently made by us, indicate the potential importance of glucocorticoid-placental interactions in the physiology of human pregnancy. The first observation was that glucocorticoid receptors were almost undetectable in first trimester placental cytosol but was 30-fold higher in cytosol from term human placenta. The question of whether the human placenta is glucocorticoid-responsive is germane since, in many other animals, glucocorticoids produce changes in placental function which initiate parturition. In order to better understand this relationship in humans we will assay placental receptors at various stages of gestation in order to define the ontogeny of the receptor more precisely. In addition placental receptor levels will be measured in examples of both delayed and pemature parturition to determine if they are abnormally low or prematurely high. Such observations may lead to new, rational therapeutic approaches to defects of parturition. Our second observation is of carrier-mediated transport of glucocorticoid into membrane vesicles isolated from term placenta. The vesicles also convert corticosterone to 11-dehydrocorticosterone. In this area our research objectives will be to fully characterize the steroid transport and enzymatic functions of the vesicles and to determine if the transport and metabolic functions of the vesicles are performed by the same protein. We believe that placental transport and metabolism of glucocorticoids is physiologically important since it is known that fetal cortisone levels are high and that greater than 90% of fetal cortisone is derived from maternal cortisol by placental transfer and metabolism. Moreover, it has been shown that some fetal tissues can convert cortisone to cortisol and thus for tissues such as the fetal lung cortisone is an active hormone. Maintenance of this "precursor" glucocorticoid (cortisone) in adequate levels may be essential for the proper fetal development of such tissues as lung which require glucocorticoids to mature. It follows then that our studies of how glucocorticoid are transported across the placental barrier are of fundamental importance to a full undertanding of the physiology of pregnancy.